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CHNG4
MCID: HYP795
MIFTS: 50

Hypothyroidism, Congenital, Nongoitrous, 4 (CHNG4)

Categories: Endocrine diseases, Genetic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes
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Aliases & Classifications for Hypothyroidism, Congenital, Nongoitrous, 4

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MalaCards integrated aliases for Hypothyroidism, Congenital, Nongoitrous, 4:

Name: Hypothyroidism, Congenital, Nongoitrous, 4 57 73
Tsh Deficiency 57 53 55
Congenital Nongoitrous Hypothyroidism 4 12 15
Thyrotropin Deficiency, Isolated 57 53
Isolated Thyrotropin Deficiency 12 59
Isolated Tsh Deficiency 59 37
Pituitary Cretinism 57 53
Chng4 57 12
Isolated Thyroid-Stimulating Hormone Deficiency 59
Hypothyroidism, Congenital, Nongoitrous, Type 4 40
Thyroid-Stimulating Hormone, Deficiency of 53
Hypothyroidism, Congenital, Nongoitrous 4 57
Thyroid-Stimulating Hormone Deficiency 57
Secondary Hypothyroidism 73

Characteristics:

Orphanet epidemiological data:

59
isolated thyroid-stimulating hormone deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
hypothyroidism, congenital, nongoitrous, 4:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Endocrine diseases Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 33 34
Orphanet: 59  
Rare endocrine diseases


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Summaries for Hypothyroidism, Congenital, Nongoitrous, 4

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Disease Ontology : 12 A congenital hypothyroidism characterized by a permanent thyroid deficiency present at birth and resulting from deficiency in TSH synthesis that has material basis in homozygous mutation in the TSHB gene on chromosome 1p13.

MalaCards based summary : Hypothyroidism, Congenital, Nongoitrous, 4, also known as tsh deficiency, is related to myxedema and conn's syndrome. An important gene associated with Hypothyroidism, Congenital, Nongoitrous, 4 is TSHB (Thyroid Stimulating Hormone Beta), and among its related pathways/superpathways are Thyroid hormone synthesis and Aldosterone synthesis and secretion. Affiliated tissues include thyroid, pituitary and heart, and related phenotypes are hypothyroidism and muscular hypotonia

Description from OMIM: 275100
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Related Diseases for Hypothyroidism, Congenital, Nongoitrous, 4

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Diseases in the Hypothyroidism, Congenital, Nongoitrous, 2 family:

Hypothyroidism, Congenital, Nongoitrous, 5 Hypothyroidism, Congenital, Nongoitrous, 4
Hypothyroidism, Congenital, Nongoitrous, 1 Hypothyroidism, Congenital, Nongoitrous, 3
Hypothyroidism, Congenital, Nongoitrous, 6

Diseases related to Hypothyroidism, Congenital, Nongoitrous, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 124)
# Related Disease Score Top Affiliating Genes
1 myxedema 29.8 TG TPO
2 conn's syndrome 29.7 CRH GH1 POMC PRL
3 adenohypophysitis 29.6 GH1 POMC PRL TRH
4 pituitary gland disease 28.8 CRH GH1 IGF1 POMC POU1F1 PRL
5 hypothyroidism 28.1 GH1 IGF1 POMC POU1F1 PRL PROP1
6 thyroid-stimulating hormone level quantitative trait locus 1 11.1
7 central congenital hypothyroidism 11.1
8 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.3 POU1F1 PROP1
9 combined pituitary hormone deficiencies, genetic forms 10.3 POU1F1 PROP1
10 fibrous dysplasia/mccune-albright syndrome 10.3 GH1 PRL
11 chiasmal syndrome 10.2 POMC PRL
12 pituitary apoplexy 10.2 POMC PRL
13 sella turcica neoplasm 10.2 POMC PRL
14 tuberculum sellae meningioma 10.2 POMC PRL
15 gigantism 10.2 GH1 PRL
16 acute thyroiditis 10.2 POMC TG
17 lymphocytic hypophysitis 10.2 GH1 POMC
18 pituitary hypoplasia 10.2 POU1F1 PRL
19 endocrine exophthalmos 10.2 POMC TG
20 galactorrhea 10.2 IGF1 PRL
21 acidophil adenoma 10.2 IGF1 POMC
22 abducens nerve disease 10.2 POMC PRL
23 mammographic density 10.2 IGF1 PRL
24 septooptic dysplasia 10.2 POU1F1 PROP1
25 generalized resistance to thyroid hormone 10.2 PRL TRH
26 marasmus 10.2 GH1 IGF1
27 diabetes insipidus, neurohypophyseal 10.2 POMC PRL
28 pituitary stalk interruption syndrome 10.2 GH1 POU1F1 PRL
29 subacute lymphocytic thyroiditis 10.2 TG TPO
30 melancholia 10.1 CRH PRL
31 familial thyroid dyshormonogenesis 10.1 TG TPO
32 neonatal hypothyroidism 10.1 TG TPO
33 goiter, multinodular 1, with or without sertoli-leydig cell tumors 10.1 TG TPO
34 gangliocytoma 10.1 CRH POMC
35 sex differentiation disease 10.1 POMC PRL
36 cone-rod dystrophy 12 10.1 GH1 IGF1
37 acth deficiency, isolated 10.1 CRH POMC
38 isolated growth hormone deficiency, type ib 10.1 GH1 IGF1
39 pituitary infarct 10.1 IGF1 POMC PRL
40 plummer's disease 10.1 TG TPO
41 premature menopause 10.1 TG TPO
42 endocrine organ benign neoplasm 10.1 IGF1 POMC PRL
43 pituitary adenoma 1, multiple types 10.1 GH1 IGF1 PRL
44 pernicious anemia 10.1 TG TPO
45 hyperandrogenism 10.1 IGF1 POMC PRL
46 spinocerebellar degeneration 10.1 CRH PRL
47 tetrahydrobiopterin deficiency 10.1 GH1 PRL
48 mccune-albright syndrome 10.1 GH1 IGF1 PRL
49 acquired metabolic disease 10.1 IGF1 POMC PRL
50 ovarian cystic teratoma 10.1 PRL TG

Graphical network of the top 20 diseases related to Hypothyroidism, Congenital, Nongoitrous, 4:



Diseases related to Hypothyroidism, Congenital, Nongoitrous, 4
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Symptoms & Phenotypes for Hypothyroidism, Congenital, Nongoitrous, 4

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Symptoms via clinical synopsis from OMIM:

57
Head And Neck Mouth:
macroglossia

Abdomen External Features:
umbilical hernia
omphalocele (rare)

Muscle Soft Tissue:
hypotonia

Growth Other:
growth retardation, severe (if untreated)

Endocrine Features:
hypothyroidism, nongoitrous

Head And Neck Nose:
depressed nasal bridge

Voice:
hoarse cry

Skeletal Skull:
large anterior fontanelle
open posterior fontanelle

Neurologic Central Nervous System:
mental retardation, severe (if untreated)

Laboratory Abnormalities:
low to normal tsh (values may vary depending on the measurement methods used)


Clinical features from OMIM:

275100

Human phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 4:

59 32 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypothyroidism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000821
2 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
3 constipation 59 32 hallmark (90%) Very frequent (99-80%) HP:0002019
4 sleep disturbance 59 32 hallmark (90%) Very frequent (99-80%) HP:0002360
5 macroglossia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000158
6 coarse facial features 59 32 hallmark (90%) Very frequent (99-80%) HP:0000280
7 umbilical hernia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001537
8 fatigue 59 32 hallmark (90%) Very frequent (99-80%) HP:0012378
9 feeding difficulties 59 32 hallmark (90%) Very frequent (99-80%) HP:0011968
10 jaundice 59 32 hallmark (90%) Very frequent (99-80%) HP:0000952
11 large fontanelles 59 32 hallmark (90%) Very frequent (99-80%) HP:0000239
12 abdominal distention 59 32 hallmark (90%) Very frequent (99-80%) HP:0003270
13 depressed nasal bridge 32 HP:0005280
14 hoarse cry 32 HP:0001615
15 intellectual disability, severe 32 HP:0010864
16 abnormality of metabolism/homeostasis 32 HP:0001939
17 intellectual disability, progressive 32 HP:0006887
18 wide anterior fontanel 32 HP:0000260
19 omphalocele 32 HP:0001539
20 generalized hypotonia 32 HP:0001290
21 severe postnatal growth retardation 32 HP:0008850
22 congenital hypothyroidism 32 HP:0000851

MGI Mouse Phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.96 CRH IGF1 PBX1 POMC POU1F1 PRL
2 growth/size/body region MP:0005378 9.85 CRH IGF1 PBX1 POMC POU1F1 PROP1
3 homeostasis/metabolism MP:0005376 9.7 CRH DMPK IGF1 PBX1 POMC POU1F1
4 nervous system MP:0003631 9.28 CRH IGF1 PBX1 POMC POU1F1 PRL
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Drugs & Therapeutics for Hypothyroidism, Congenital, Nongoitrous, 4

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Search Clinical Trials , NIH Clinical Center for Hypothyroidism, Congenital, Nongoitrous, 4

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Genetic Tests for Hypothyroidism, Congenital, Nongoitrous, 4

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Anatomical Context for Hypothyroidism, Congenital, Nongoitrous, 4

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MalaCards organs/tissues related to Hypothyroidism, Congenital, Nongoitrous, 4:

41
Thyroid, Pituitary, Heart, Brain, T Cells, Cortex, Adrenal Gland
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Publications for Hypothyroidism, Congenital, Nongoitrous, 4

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Articles related to Hypothyroidism, Congenital, Nongoitrous, 4:

(show all 13)
# Title Authors Year
1
Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans. ( 21123951 )
2011
2
Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine. ( 21521256 )
2011
3
Longitudinal study of patients with idiopathic isolated TSH deficiency: possible progression of pituitary dysfunction in lymphocytic adenohypophysitis. ( 16896268 )
2006
4
GH and TSH deficiency. ( 9439906 )
1997
5
A case of idiopathic thyrotropin (TSH) deficiency. ( 9159047 )
1997
6
Isolated TSH deficiency with a partially empty sella. ( 8719305 )
1995
7
A case of isolated TSH deficiency presenting as infertility. ( 8183759 )
1994
8
Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit. ( 2792087 )
1989
9
Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit. ( 16453906 )
1989
10
Adrenal catecholamine content: effects of congenital GH, PRL and TSH deficiency and of hormone replacement therapy in the male mouse. ( 3758194 )
1986
11
Isolated ACTH deficiency and TSH deficiency in the adult. ( 233250 )
1979
12
Isolated TSH deficiency presenting as myxedema heart disease. ( 4253518 )
1971
13
Isolated thyroid-stimulating hormone (TSH) deficiency following childbirth. ( 4163013 )
1966
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Variations for Hypothyroidism, Congenital, Nongoitrous, 4

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ClinVar genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 4:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 TSHB NM_000549.4(TSHB): c.145G> A (p.Gly49Arg) single nucleotide variant Pathogenic rs121918668 GRCh37 Chromosome 1, 115576128: 115576128
2 TSHB NM_000549.4(TSHB): c.145G> A (p.Gly49Arg) single nucleotide variant Pathogenic rs121918668 GRCh38 Chromosome 1, 115033507: 115033507
3 TSHB NM_000549.4(TSHB): c.94G> T (p.Glu32Ter) single nucleotide variant Pathogenic rs121918669 GRCh37 Chromosome 1, 115576077: 115576077
4 TSHB NM_000549.4(TSHB): c.94G> T (p.Glu32Ter) single nucleotide variant Pathogenic rs121918669 GRCh38 Chromosome 1, 115033456: 115033456
5 TSHB TSHB, 1-BP DEL, 313T deletion Pathogenic
6 TSHB NM_000549.4(TSHB): c.205C> T (p.Gln69Ter) single nucleotide variant Pathogenic rs121918670 GRCh37 Chromosome 1, 115576636: 115576636
7 TSHB NM_000549.4(TSHB): c.205C> T (p.Gln69Ter) single nucleotide variant Pathogenic rs121918670 GRCh38 Chromosome 1, 115034015: 115034015
8 TSHB TSHB, IVS2, G-A, +5 single nucleotide variant Pathogenic
9 TSHB NM_000549.4(TSHB): c.40A> G (p.Thr14Ala) single nucleotide variant Benign rs10776792 GRCh38 Chromosome 1, 115033402: 115033402
10 TSHB NM_000549.4(TSHB): c.40A> G (p.Thr14Ala) single nucleotide variant Benign rs10776792 GRCh37 Chromosome 1, 115576023: 115576023
11 TSHB NM_000549.4(TSHB): c.373delT (p.Cys125Valfs) deletion Pathogenic/Likely pathogenic rs755485552 GRCh37 Chromosome 1, 115576804: 115576804
12 TSHB NM_000549.4(TSHB): c.373delT (p.Cys125Valfs) deletion Pathogenic/Likely pathogenic rs755485552 GRCh38 Chromosome 1, 115034183: 115034183
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Expression for Hypothyroidism, Congenital, Nongoitrous, 4

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Search GEO for disease gene expression data for Hypothyroidism, Congenital, Nongoitrous, 4.
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Pathways for Hypothyroidism, Congenital, Nongoitrous, 4

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Pathways related to Hypothyroidism, Congenital, Nongoitrous, 4 according to KEGG:

37
# Name Kegg Source Accession
1 Thyroid hormone synthesis hsa04918

Pathways related to Hypothyroidism, Congenital, Nongoitrous, 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Aldosterone synthesis and secretion 37
Show member pathways
 12.11 PBX1 POMC SERPINA7 TG TPO TSHB
2
Peptide hormone metabolism 66
Show member pathways
 11.82 GH1 IGF1 POMC TSHB
3
G alpha (s) signalling events 66
11.71 CRH POMC TSHB
4
Glucocorticoid receptor regulatory network 1
11.37 PBX1 POMC POU1F1 PRL
5
Development_Leptin signaling via JAK/STAT and MAPK cascades 22
Show member pathways
 10.88 POMC TRH
6
Glucocorticoid Pathway (HPA Axis), Pharmacodynamics 61
10.17 CRH POMC
7
Thyroxine (Thyroid Hormone) Production 1
9.58 TG TPO TRH
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GO Terms for Hypothyroidism, Congenital, Nongoitrous, 4

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Cellular components related to Hypothyroidism, Congenital, Nongoitrous, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.56 CRH GH1 IGF1 POMC PRL SERPINA7
2 secretory granule GO:0030141 9.33 POMC PRL TRH
3 extracellular region GO:0005576 9.28 CRH GH1 IGF1 POMC PRL SERPINA7
4 endosome lumen GO:0031904 9.26 GH1 PRL

Biological processes related to Hypothyroidism, Congenital, Nongoitrous, 4 according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 response to ethanol GO:0045471 9.65 CRH PRL TRH
2 regulation of multicellular organism growth GO:0040014 9.55 IGF1 PRL
3 positive regulation of cell proliferation GO:0008284 9.55 CRH IGF1 PBX1 POU1F1 PRL
4 positive regulation of JAK-STAT cascade GO:0046427 9.54 GH1 PRL
5 adrenal gland development GO:0030325 9.52 CRH PBX1
6 response to corticosterone GO:0051412 9.51 CRH TRH
7 embryonic hemopoiesis GO:0035162 9.49 PBX1 TPO
8 regulation of ossification GO:0030278 9.46 PBX1 PRL
9 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.43 GH1 PRL
10 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.4 GH1 IGF1
11 hormone biosynthetic process GO:0042446 9.37 TG TPO
12 parturition GO:0007567 9.32 CRH PRL
13 adenohypophysis development GO:0021984 9.26 POU1F1 PROP1
14 regulation of signaling receptor activity GO:0010469 9.17 GH1 IGF1 POMC PRL TG TRH
15 somatotropin secreting cell differentiation GO:0060126 8.96 POU1F1 PROP1

Molecular functions related to Hypothyroidism, Congenital, Nongoitrous, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 9.23 CRH GH1 IGF1 POMC PRL TG
2 prolactin receptor binding GO:0005148 8.96 GH1 PRL
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Sources for Hypothyroidism, Congenital, Nongoitrous, 4

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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